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Types of Cancer > Skin Cancers > Melanoma > NCI Resources

NCI/PDQ^® Health professionals: Melanoma Treatment (PDQ®)

Affiliation: National Cancer Institute
Last Modified: July 1, 2009

TABLE OF CONTENTS

• Purpose of This PDQ® Summary

• General Information

• Cellular Classification

• Stage Information
  • Clark Classification (Level of Invasion)
  • TNM Definitions
  • Clinical Staging
    • AJCC stage groupings
  • Pathologic Staging
    • AJCC stage groupings

• Treatment Option Overview

• Stage 0 Melanoma
  • Current Clinical Trials

• Stage I Melanoma
  • Current Clinical Trials

• Stage II Melanoma
  • Current Clinical Trials

• Stage III Melanoma
  • Current Clinical Trials

• Stage IV Melanoma
  • Current Clinical Trials

• Recurrent Melanoma
  • Current Clinical Trials

• Get More Information From NCI

• Changes to This Summary (07/01/2009)

• More Information

Purpose of This PDQ® Summary

This PDQ® cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of melanoma. This summary is reviewed regularly and updated as necessary by the PDQ® Adult Treatment Editorial Board.

Information about the following is included in this summary:

• Prognostic factors.
• Cellular classification.
• Staging.
• Treatment options by cancer stage.

This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ® Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either standard or under clinical evaluation. These classifications should not be used as a basis for reimbursement determinations.

This summary is available in a patient version, written in less technical language, and in Spanish.

General Information

Note: Separate PDQ® summaries on Skin Cancer Treatment; Skin Cancer Prevention; and Skin Cancer Screening are also available.

Note: Estimated new cases and deaths from melanoma in the United States in 2009: 1

• New cases: 68,720.
• Deaths: 8,650.

Melanoma is a malignant tumor of melanocytes, which are the cells that make the pigment melanin and are derived from the neural crest. Although most melanomas arise in the skin, they may also arise from mucosal surfaces or at other sites to which neural crest cells migrate. Melanoma occurs predominantly in adults, and more than 50% of the cases arise in apparently normal areas of the skin. Early signs in a nevus that would suggest malignant change include darker or variable discoloration, itching, an increase in size, or the development of satellites. Ulceration or bleeding are later signs. Melanoma in women occurs more commonly on the extremities and in men on the trunk or head and neck, but it can arise from any site on the skin surface. A biopsy, preferably by local excision, should be performed for any suspicious lesions, and the specimens should be examined by an experienced pathologist to allow for microstaging. Suspicious lesions should never be shaved off or cauterized. Studies show that distinguishing between benign pigmented lesions and early melanomas can be difficult, and even experienced dermatopathologists can have differing opinions. To reduce the possibility of misdiagnosis for an individual patient, a second review by an independent qualified pathologist should be considered. 2

Prognosis is affected by clinical and histological factors and by anatomic location of the lesion. Thickness and/or level of invasion of the melanoma, mitotic index, presence of tumor infiltrating lymphocytes, number of regional lymph nodes involved, and ulceration or bleeding at the primary site affect the prognosis. 3 4 5 6 Microscopic satellites in stage I melanoma may be a poor prognostic histologic factor, but this is controversial. 7 Patients who are younger, female, and who have melanomas on the extremities generally have a better prognosis. 3 4 5 6

Clinical staging is based on whether the tumor has spread to regional lymph nodes or distant sites. For disease clinically confined to the primary site, the greater the thickness and depth of local invasion of the melanoma, the higher the chance of lymph node or systemic metastases and the worse the prognosis. Melanoma can spread by local extension (through lymphatics) and/or by hematogenous routes to distant sites. Any organ may be involved by metastases, but lungs and liver are common sites. The risk of relapse decreases substantially over time, though late relapses are not uncommon. 8 9

References:

1. American Cancer Society.: Cancer Facts and Figures 2009. Atlanta, Ga: American Cancer Society, 2009. Also available online [PUBMED Abstract]
2. Corona R, Mele A, Amini M, et al.: Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions. J Clin Oncol 14 (4): 1218-23, 1996. [PUBMED Abstract]
3. Balch CM, Soong S, Ross MI, et al.: Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup Melanoma Surgical Trial. Ann Surg Oncol 7 (2): 87-97, 2000. [PUBMED Abstract]
4. Manola J, Atkins M, Ibrahim J, et al.: Prognostic factors in metastatic melanoma: a pooled analysis of Eastern Cooperative Oncology Group trials. J Clin Oncol 18 (22): 3782-93, 2000. [PUBMED Abstract]
5. Balch CM, Buzaid AC, Soong SJ, et al.: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19 (16): 3635-48, 2001. [PUBMED Abstract]
6. Liu ZJ, Herlyn M: Melanoma. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1745-1824. [PUBMED Abstract]
7. León P, Daly JM, Synnestvedt M, et al.: The prognostic implications of microscopic satellites in patients with clinical stage I melanoma. Arch Surg 126 (12): 1461-8, 1991. [PUBMED Abstract]
8. Shen P, Guenther JM, Wanek LA, et al.: Can elective lymph node dissection decrease the frequency and mortality rate of late melanoma recurrences? Ann Surg Oncol 7 (2): 114-9, 2000. [PUBMED Abstract]
9. Tsao H, Cosimi AB, Sober AJ: Ultra-late recurrence (15 years or longer) of cutaneous melanoma. Cancer 79 (12): 2361-70, 1997. [PUBMED Abstract]

Cellular Classification

Following is a list of clinicopathologic cellular subtypes of malignant melanoma. These should be considered descriptive terms of historic interest only as they do not have independent prognostic or therapeutic significance.

• Superficial spreading.
• Nodular.
• Lentigo maligna.
• Acral lentiginous (palmar/plantar and subungual).
• Miscellaneous unusual types:
  • Mucosal lentiginous (oral and genital).
  • Desmoplastic.
  • Verrucous.

Stage Information

Agreement between pathologists in the histologic diagnosis of melanomas and benign pigmented lesions has been studied and found to be considerably variable. One such study found that there was discordance on the diagnosis of melanoma versus benign lesions in 37 of 140 cases examined by a panel of experienced dermatopathologists. 1 For the histologic classification of cutaneous melanoma, the highest concordance was attained for Breslow thickness and presence of ulceration, while the agreement was poor for other histologic features such as Clark level of invasion, presence of regression, and lymphocytic infiltration. In another study, 38% of cases examined by a panel of expert pathologists had two or more discordant interpretations. These studies convincingly show that distinguishing between benign pigmented lesions and early melanoma can be difficult, and even experienced dermatopathologists can have differing opinions. To reduce the possibility of misdiagnosis for an individual patient, a second review by an independent qualified pathologist should be considered. 2

The microstage of malignant melanoma is determined on histologic examination by the vertical thickness of the lesion in millimeters (Breslow classification) and/or the anatomic level of local invasion (Clark classification). The Breslow thickness is more reproducible and more accurately predicts subsequent behavior of malignant melanoma in lesions larger than 1.5 mm in thickness and should always be reported. Accurate microstaging of the primary tumor requires careful histologic evaluation of the entire specimen by an experienced pathologist. Estimates of prognosis should be modified by sex and anatomic site as well as by clinical and histologic evaluation.

Clark Classification (Level of Invasion)

• Level I: Lesions involving only the epidermis (in situ melanoma); not an invasive lesion.
• Level II: Invasion of the papillary dermis but does not reach the papillary-reticular dermal interface.
• Level III: Invasion fills and expands the papillary dermis but does not penetrate the reticular dermis.
• Level IV: Invasion into the reticular dermis but not into the subcutaneous tissue.
• Level V: Invasion through the reticular dermis into the subcutaneous tissue.

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define melanoma. 3

TNM Definitions

Primary tumor (T)
• TX: Primary tumor cannot be assessed (e.g., shave biopsy or regressed melanoma)
• T0: No evidence of primary tumor
• Tis: Melanoma in situ
• T1: Tumor 1.0 mm or less in thickness with or without ulceration
  • T1a: Tumor 1.0 mm or less in thickness and Clark level II or III with no ulceration
  • T1b: Tumor 1.0 mm or less in thickness and Clark level IV or V or with ulceration

• T2: Tumor more than 1.0 mm but 2.0 mm or less in thickness with or without ulceration
  • T2a: Tumor more than 1.0 mm but 2.0 mm or less in thickness with no ulceration
  • T2b: Tumor more than 1.0 mm but 2.0 mm or less in thickness with ulceration

• T3: Tumor more than 2.0 mm but 4.0 mm or less in thickness with or without ulceration
  • T3a: Tumor more than 2.0 mm but 4.0 mm or less in thickness without ulceration
  • T3b: Tumor more than 2.0 mm but 4.0 mm or less in thickness with ulceration

• T4: Tumor more than 4.0 mm in thickness with or without ulceration
  • T4a: Tumor more than 4.0 mm in thickness without ulceration
  • T4b: Tumor more than 4.0 mm in thickness with ulceration

Regional lymph nodes (N)
• NX: Regional lymph nodes cannot be assessed
• N0: No regional lymph node metastasis
• N1: Metastasis to one lymph node
  • N1a: Clinically occult (microscopic) metastasis
  • N1b: Clinically apparent (macroscopic) metastasis

• N2: Metastasis to two or three regional nodes or intralymphatic regional metastasis without nodal metastases
  • N2a: Clinically occult (microscopic) metastasis
  • N2b: Clinically apparent (macroscopic) metastasis
  • N2c: Satellite or in-transit metastasis without nodal metastasis

• N3: Metastasis in more than four regional nodes, or matted lymph nodes, or in-transit metastasis or satellite(s) with metastatic regional node(s)

  [Note: Micrometastases are diagnosed after elective or sentinel lymphadenectomy; macrometastases are defined as clinically detectable lymph nodes metastases confirmed by therapeutic lymphadenectomy, or when any lymph node metastasis exhibits gross extracapsular extension.]

Distant Metastasis (M)
• MX: Distant metastasis cannot be assessed
• M0: No distant metastasis
• M1: Distant metastasis
  • M1a: Metastasis to skin, subcutaneous tissues, or distant lymph nodes
  • M1b: Metastasis to lung
  • M1c: Metastasis to all other visceral sites or distant metastasis at any site associated with an elevated serum lactic dehydrogenase